Fig. 1

TERT levels affect EBV latent/lytic status. A, cross-talk between EBV and TERT to sustain viral latency program: in EBV-infected primary B lymphocytes, activation of TERT occurs concomitantly with induction of latent EBV proteins and down-regulation of EBV lytic gene expression. EBV-encoded LMP-1 activates TERT at transcriptional level via NF-κB and MAPK/ERK1/2 pathways. In turn, TERT expression activates NOTCH2 at transcriptional level via NF-κB pathway. NOTCH2 activates BATF, which negatively affects the expression of BZLF1, a master regulator of viral lytic cycle, thus favouring induction and maintenance of EBV latency program, essential for EBV-driven transformation. Immunohistochemical image: TERT (a, b) and BZLF1 (c, d) protein expression in early- (a, c) and late- (b, d) infected B lymphocytes (X40). B, TERT or NOTCH inhibition triggers EBV lytic cycle: TERT silencing by shRNA (shTERT) or inhibition of NOTCH signaling by γ-secretase inhibitors lead to NOTCH2-dependent down-regulation of BATF and up-regulation of BZLF1, inducing a complete EBV lytic cycle. Immunohistochemical image: EBV lytic gp350 protein expression in EBV-positive BL cells untreated (a) and treated (b) for 72 h with shTERT (X20). Scale bar, 100 μm. See the text for details